Following radical treatment for prostate cancer (PCa), men who carry BRCA gene mutations have worse outcomes than non-carriers, according to new findings.
BRCA mutation carriers treated at diagnosis with curative intent by radical prostatectomy (RP) or radiotherapy (RT) are more likely to develop metastasis and to die from PCa, researchers reported.
“Pending future studies confirming the biologic role of BRCA genetic alternations in this setting, our results support closer follow-up of these patients and the need for clinical trials to tailor the best radical/adjuvant treatments,” the authors, led by Elena Castro, MD, of the Spanish National Cancer Research Institute in Madrid, wrote in a paper published online ahead of print in European Urology.
Dr. Castro and her colleagues studied 1,302 men with local or locally advanced PCa, including 67 BRCA mutation carriers. Of these patients, 535 underwent RP, including 35 BRCA mutation carriers, and 767 received RT, including 32 BRCA mutation carriers. Subjects had a median follow-up was 64 months.
At 3, 5, and 10 years after treatment, 90%, 72%, and 50% of carriers, respectively, were free from metastasis compared with 97%, 94%, and 84% of noncarriers. The 3-, 5-, and 10-year cancer-specific survival rates were significantly worse in the carrier than noncarrier cohort (96%, 76%, and 61% vs. 99%, 97%, and 85%, respectively).
In multivariate analysis, BRCA mutations independently predicted a nearly 2.4 times increased risk of developing metastatic disease and 2.2 times increased risk of PCa-related death, Dr. Castro and her colleagues reported.
“Despite our results,” they wrote, “the screening of unselected patients for germline BRCA mutations is not justified due to the current cost of the procedure and the low frequency of those events in sporadic PCa.”
They pointed out, however, that as technologies evolve and the cost of sequencing genomes and specific gene panels continues to decrease, screening for BRCA mutations may prove cost-effective, especially if additional studies support the need of personalized therapy for patients with germline and/or somatic BRCA alterations.